As several siRNA therapeutics move toward regulatory approval for cardiometabolic diseases, we expect demand for large-scale manufacturing to grow sharply over the coming decade.
At TIDES Europe 2025 in Basel, our CTO, David Butler, spoke about the limitations of traditional solid-phase oligonucleotide synthesis in meeting that demand at the scale, cost, and level of sustainability the field will require.
The presentation focused on chemoenzymatic ligation, a next-generation manufacturing approach for producing high-purity siRNA more efficiently at a larger scale. Two case studies demonstrated how this approach can 1) support complex formats such as multivalent siRNAs, and 2) reduce manufacturing costs by eliminating chromatography from the process.
Dave highlighted the importance of engineered thermostable ligases in improving process performance and enabling future scale-up. In addition, he covered key CMC and regulatory considerations for bringing this technology into clinical development, including the exciting recent announcement that we have completed cGMP manufacturing of a GalNAc-siRNA conjugate targeting PCSK9 for use in human dosing.
